Our lab uses a variety of techniques to study the function and the structure of neural circuits. In our mouse studies, we study the roles of neuron subtypes that make up these circuits using genetically engineered mouse lines and viral vectors. We then modulate these specific neuron subtypes using optogenetics, chemogenetics, or selective deletion tools, which we combine with detailed analyses of muscle signals (EMG), electrical recordings of brain activity (EEG), or activity of populations of neurons using calcium imaging. We visualize and reconstruct the circuits using neuron subtype specific and conventional anterograde and retrograde tracers.
We pair these assays with functional outcome measures that are not only valid in mouse models but which are translatable to human models. For example, we have developed and validated an approach for analysis of walking gait that allows for translation of walking gait metrics between quadruped mice and biped human subjects.
While we cannot study the same neural circuits in human subjects as directly as we can in mice, we do measure similar functions using wearable device technology or other tools. We then correlate (dys)function with location and burden of neurodegenerative disease or cell loss in neural circuits that we can examine in more details in mouse models.
In both mouse and human study lines, we integrate circuit structure and mapping using conventional and multiplex immunohistochemistry and in situ hybridization in combination with state of the art tissue imaging and image analyses to determine the neurochemical and molecular properties of nerve cells and nerve fiber endings in these circuits and across disease conditions.